Capsosiphon fulvescens glycoprotein inhibits AGS gastric cancer cell proliferation by downregulating Wnt-1 signaling

Int J Oncol. 2013 Nov;43(5):1395-401. doi: 10.3892/ijo.2013.2079. Epub 2013 Aug 23.

Abstract

Previously, we examined various apoptosis pathways in the AGS gastric cancer cell line using Capsosiphon fulvescens glycoprotein (Cf-GP). In this study, we focused on the downregulation of the Wnt-1 signaling pathway and cell cycle arrest. Upregulation of the Wnt signaling pathway has been observed in various cancer cells. The Wnt signal ligand acts in both canonical and non-canonical pathways. Among them, Wnt-1 was dependent on the canonical pathway. Here, we show inhibition of Wnt-1 signaling, β-catenin and transcription factors in AGS cells via Cf-GP. First, we examined the Frizzled receptor and Wnt-1 signal-related proteins including Axin, LRP, β-catenin, APC and GSK-3β. In addition, the expression levels of transcription factors Tcf/LEF were determined by western blot analysis and RT-PCR. Based on the data, we confirmed downregulation of the Wnt-1 signaling pathway by Cf-GP. Also, we determined the expression levels of cell cycle-related proteins cyclin D and c-myc, and looked for cell cycle arrest by cell cycle test analysis. We found that AGS cells arrested in the G0/G1 phase by Cf-GP. These results provide a mechanism of AGS cell inhibition through the downregulation of Wnt-1 signaling by Cf-GP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Blotting, Western
  • Cell Adhesion / drug effects
  • Cell Cycle / drug effects
  • Cell Proliferation / drug effects*
  • Chlorophyta / chemistry*
  • Down-Regulation
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Glycoproteins / metabolism*
  • Humans
  • Plant Extracts / pharmacology*
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology
  • Stomach Neoplasms / prevention & control*
  • Tumor Cells, Cultured
  • Wnt1 Protein / antagonists & inhibitors*
  • Wnt1 Protein / genetics
  • Wnt1 Protein / metabolism

Substances

  • Glycoproteins
  • Plant Extracts
  • RNA, Messenger
  • WNT1 protein, human
  • Wnt1 Protein